Norman Shumway is widely regarded as the father of heart transplantation although the world's first adult human heart transplant was performed by Christiaan Barnard, on December 3, 1967, at the Groote Schuur Hospital in Cape Town, South Africa. Adrian Kantrowitz performed the world's first pediatric heart transplant on December 6, 1967 and Norman Shumway performed the first adult heart transplant in the United States on January 6, 1968, at the Stanford University Hospital. In India, PK Sen attempted the first heart transplant in humans soon after Christaan Barnaard but the first and subsequent patients died. The first successful heart transplant in India was by Dr. P Venugopal in 1994 at AIIMS, New Delhi. This was followed soon after by Dr. KM Cherian who also did the first pediatric and first heart lung transplant in India.

“That's all we ever really wanted in the end. It would have been great to be first, but, finally, what always mattered most was that we'd find a way to help people live a little longer so that they could be with those they loved, and do the things they cared about, for a little longer. It was a very simple hope, but we did it. That seems the best memento of all. I'm happy to make an anniversary of that fact.”

–Shumway

Human instincts acknowledge “being first”in every sphere from science to the arts. History too distinctively remembers individuals who did it (any invention/discovery or achievement) for the first time. There is always a phenomenal history behind every first doing, sometimes unsung or unheard. This article intends to bring together the history of the heart transplant, both the global and Indian perspective. It discusses a series of events across the years, which framed the current platform for heart transplant surgeries and the pioneers behind and on the scenes. The story has been built upon tireless efforts and sacrifices.

The world's first heart transplant was applauded and gained attention at once. Simultaneous similar attempts were made in different parts of the world. Initial endeavors were not successful which can be attributed to the less understood biology of cardiac transplantation at that time.

the Initial Attempts

In the 1890s, Alexis Carrel began experiments with vascular anastomosis. He also tried the initial heart transplants by connecting the carotid arteries of dogs to the donor aortas.[1],[2],[3] In the 1930s, at Mayo Clinic, Mann and his team also tried similar kinds of surgical implants. The first major step came from Russia when Demikhov managed to do transplants in dogs with an end-to-end aorta anastomosis. In 1951, Marcus and his team reported on their experiments with heterotopic heart transplants from Chicago.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]

The increase in pace in research came with the reports of orthotopic heart transplant experiments in dogs from Lower and Shumway's group. Their dogs survived for up to 21 days.[15],[16],[17],[18],[19],[20]

The transformation phase in the history of terminally ill patients was brought in the period of the 1960s. That era saw a magnificent medical achievement both from the perspective of patients and doctors worldwide, opening the avenues for a better tomorrow. The first transplant was animal to the human heart and eventually human to human heart replacement was performed.

on Animals

The first animal (chimpanzee) to human heart transplant in the world was performed by James Hardy at the University of Mississippi Medical Center in Jackson on January 23, 1964. James Hardy had chosen a patient with the extensive vascular disease with amputations of both legs, who was semicomatose and was dying. However, the chimpanzee heart was not large enough to support the circulation and failed soon after [Figure 1].[21]

The next famous attempt at xenotransplant was by Bailey in 1983 when he attempted to transplant a baboon heart to an infant girl, known as “Baby Fae.” The surgery was technically successful, but there was an acute rejection, and the girl died 20 days later.[22]

Unveiling the Story of “ditgaanwerk:” Story behind Closed Doors

The inclination for replacing the failing heart with another had been intriguing many surgeons around the globe around the same period. Christiaan Barnard was the first surgeon to perform human-to-human heart transplant surgery in South Africa on 3rd December 1967. A book titled “100 Headlines That Changed the World” includes the first transplant story of Washkansky under the heading of “Man with a new heart.” However, the relentless work had been undergoing much before that monumental day; it had become like a race to be the “ first.”

There has been pioneering work of surgeons who deserve appropriate recognition. Many surgeons, including Barnard, Richard Lower, Adrian Kantrowitz, and Shumway, were in the race to do a heart transplant for the first time.[22],[23],[24],[25]

While Lower, Shumway, and Kantrowitz made preparations to conduct the first heart transplant, they got delayed due to disagreements over legal and medical issues over cardiac death versus brain death. During this period, Barnard conducted the first successful human transplantation in South Africa on December 3, 1967. Adrian Kantrowitz subsequently conducted a transplant on December 6, 1967, Shumway on January 6, 1968, and Lower in May of 1968.

The story started at the University of Minnesota, where Shumway and Barnard were peers and the latter closely understanding the work of the former. The race to be the first was driving Barnard within. He performed his first successful kidney transplant in South Africa to understand transplant immunology and geared for a heart transplant. Both awaited the major components of transplant procedure – a recipient and a donor so that the first transplant could be planned. On September 14, 1967, Louis Washkansky who was a grocer by profession got admitted in the Groote Schuur Hospital in Cape Town, South Africa. Chief cardiologist Dr. Velva Schrire was aware of Barnard's interests and recommended Washkansky as the appropriate case for transplant. The patient was already suffering with diabetes and heart ailment. He seemed to be the apt recipient of the heart transplant, which raised hopes to find a donor before the situation worsened. However, the dawn came upon finding a donor on December 2, 1967, when Denise was declared brain dead. She was brought to the hospital after a road mishap. Within theaters A and B where both were operated, it was finalized with mutual consent to consider them for the first ever attempt [Figure 2].

On December 3, 1967, Barnard performed the world's first successful heart transplant. The initial recovery after surgery was good, but subsequently he worsened and was treated for a possible rejection the medical condition being actually a severe pneumonia. He succumbed on the 18th postoperative day. The second transplant patient lived for 19 months and died of severe coronary artery disease. At this point, many countries in the world over started doing heart transplants but with most patients dying soon and a 1 year survival of only 11%, very few centers continued to do heart transplants. Ten heart transplants were performed at Groote Schuur Hospital and the longest lived for 23 years.

After The first Transplant

After the first transplant, surgeons all around the world started doing the transplant, focusing on the surgery but not trying to understand the transplant immunology. Most of the one hundred patients died, and heart transplant fell into disrepute with most centers stop transplanting. Only Shumway's team continued. They worked on transplant immunology, transplant infections, efforts to improve the donor pool, improvements in organ preservation and heart biopsies, and looked at advances in drugs to prevent rejection. They were the first at Stanford to introduce cyclosporine in the late 1980s.

When Shumway restarted heart transplants, the success rates were good, and before he retired, he had overseen more than 800 transplants [Figure 3].[26],[27],[28],[29],[30]

Lower worked initially with Shumway and later left for Virginia. He performed his first transplant in May 1968. He also developed the technique of sending teams for heart harvesting to remote areas, thus reducing the need to shift the donor to the recipient hospital [Figure 4].

India holds an important place in this field. Dr. Profulla Kumar Sen became the first surgeon in India to do a heart transplant at KEM Hospital in Mumbai. He performed the world's 6th heart transplant, but his work was hampered in those early days of cardiac transplantation by the absence of a law on brain death. Unfortunately, the right heart ballooned within 15 min of coming off bypass and the patient died within 3 h. He attempted another transplant months later but that patient also died within 14 h with severe pulmonary hypertension. There were no further attempts for a long time due to the absence of a law of brain death [Figure 5].

The next era of the heart transplant in India started with the law on brain death following which on August 3, 1994, the first successful heart transplant in India was done at AIIMS by Dr. P Venogopal [Figure 6].[31]

“Legislation of brain death materialized in 1994 but the Bill had been introduced in Parliament 7 years back and we knew it was a matter of time before it was passed,” said Dr. P Venugopal. “So we had been working on the transplant program for the past 3 years.” On August 3, 1994, when they got a donor - a woman in her mid-30s who was brain dead, and whose relatives were willing to donate her heart – they had a recipient ready at AIIMS, New Delhi. “Since the donor's blood group was B + ve and the recipient was AB + ve (universal recipient) there was no problem,” said Dr. Venugopal. The recipient lived for about 14 years.

The transplant team at the AIIMS lead by Dr. Balram Airan continued the work after Dr. Venugopal retired, led by Dr. BalramAiran and had completed 47 transplants by 2016 [Figure 7].

A 30-year-old Hemalatha Soundarrajan was knocked down while crossing the road near Pallavaram. She was declared brain dead at the hospital. Her husband was willing to donate her heart. Cherian was contacted. Cherian then scoured private hospitals in Chennai, Cochin, Trivandrum, and even Hyderabad looking for a suitable recipient. Finally, he found the recipient in Chennai. General Hospital: Maimoon Beevi, 38, from Tambaram, with dilated cardiomyopathy and had been waiting for a donor heart. The surgery was successful. Vijaya Hospital provided Beevi with immunosuppressant drugs for the 1st year free of cost. A friend of Dr. Cherian from Bahrain footed the bill for the next year. All her subsequent investigations were also done free of cost.

However, after this great start, both in North and South India, there was a lull. From 1994 till date, India has done only 250 heart transplants. The numbers were far and few in the initial years as few centers were doing heart transplants due to the costs involved, as well as the lack of donors. Of late, the numbers are picking up with both an increase in the number of centers involved in heart transplant programs, as well as increase in a number of donors following an active interest by various NGOs. [Table 1] lists some of the high points of heart transplantation in India and around the world.

In India, a number of transplants have been low and very few centers have picked up this technique. Over 250 transplants have been done in India so far. Thereafter, the technique is now gradually spreading to more centers across India with major centers in Delhi, Chennai, Kochi, and Hyderabad. With time, the numbers should increase.